Investigate Effect on Mean IMT of Probucol And/or CilosTazol in Patients With Coronary Heart dIsease Taking HMGCoA Reductase Inhibitor Therapy (IMPACT on IMT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Seoul National University Hospital
Sponsor:
Collaborator:
Korea Otsuka Pharmaceutical Co.,Ltd.
Information provided by:
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01291641
First received: January 31, 2011
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to evaluate the additional effect of probucol or concomitant administration of cilostazol and probucol on mean carotid artery intima-media thickness (mean IMT) at year 1, 2, and 3.


Condition Intervention
Hyperlipidemias
Drug: HMGCoA reductase inhibitor
Drug: HMGCoA reductase inhibitor + probucol
Drug: HMGCA reductase inhibitor + probucol + cilostazol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigate Effect on Mean IMT of Probucol And/or CilosTazol in Patients With Coronary Heart dIsease Taking HMGCoA Reductase Inhibitor Therapy (IMPACT on IMT): A Randomized, Multicenter, Multinational Study

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Difference of Carotid artery IMT (mean IMT) between screening and treatment completion(3 years after) or discontinuation [ Time Frame: Baseline(screening), 3years ] [ Designated as safety issue: No ]
    For primary endpoint of Carotid artery IMT, t-test will be conducted for the mean IMT and variation by treatment arm(Group A vs B, Group A vs C). The 2-sided significance level is 5%. Morever, Mantel - Haenszel method can be accepted considering stratification factor or Sub-analysis can be done by each stratum in case of categorical variables.


Secondary Outcome Measures:
  • Time from enrollment date to the onset of composite cerebrovascular events [ Time Frame: enrollment date, onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    1. Cardiovascular death
    2. Myocardial infarction
    3. Cerebral infarction
    4. Unstable angina and cardiac failure, required hospitalization
    5. Coronary revascularization, required hospitalization
    6. PCI and coronary artery bypass grafting [CABG]

    Kaplan-Meier method will be conducted for the time from enrollment date to the onset of composite cerebrovascular and cardiovascular events by treatment arm(Group A vs B, Group A vs C). Overall survival curves and progression-free survival curves are estimated per treatment arm.


  • Number of composite cerebrovascular and cardiovascular events(including intervention) [ Time Frame: enrollment date, onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    1. Cardiovascular death
    2. Myocardial infarction
    3. Cerebral infarction
    4. Unstable angina and cardiac failure, required hospitalization
    5. Coronary revascularization, required hospitalization
    6. PCI and coronary artery bypass grafting [CABG]

    For the number of composite cerebrovascular and cardiovascular events (including intervention) t-test will be done by treatment arm(Group A vs B, Group A vs C).


  • The change of Biomarkers(1) [ Time Frame: enrollment date ,onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    Metabolic index: Lipid profile (TC, LDL-C, HDL-C, TG)

  • The change of Biomarkers(2) [ Time Frame: enrollment date ,onset date(during study period, 3years) ] [ Designated as safety issue: No ]
    Inflammatory index: High sensitive C-reactive protein (hsCRP)

  • The change of Biomarkers(3) [ Time Frame: enrollment date ,onset date(during study period, 3years) ] [ Designated as safety issue: No ]

    Oxidation index:oxidized LDL

    The change of biomarkers, t-test will be done by treatment arm(Group A vs B, Group A vs C).



Estimated Enrollment: 342
Study Start Date: March 2011
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
HMGCoA reductase inhibitor continued
Drug: HMGCoA reductase inhibitor

During the study period, HMGCoA reductase inhibitor is continuously administered to the patients.

Dosage regimen: following the package insert of each HMGCoA reductase inhibitor

Experimental: Group B
HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID
Drug: HMGCoA reductase inhibitor + probucol

In addition to the continued HMGCoA reductase inhibitor treatment, probucol is administered.

Dosage regimen: probucol 250-mg tablet, oral administration twice daily with meal(breakfast and dinner)

Experimental: Group C
HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID + Cilostazol 100 mg PO, BID
Drug: HMGCA reductase inhibitor + probucol + cilostazol

In addition to the continued HMGCoA reductase inhibitor treatment, probucol and cilostazol are administered.

Dosage regimen: probucol 250-mg tablet, oral administration twice daily with meal(breakfast and dinner) Cilostazol 100-mg tablet, twice daily by the oral route


Detailed Description:

Hyperlipidemic patients who are currently receiving HMGCoA reductase inhibitors(Statins) will be randomized Group A(Control), Group B(Probucol only added group) or Group C(Probucol and cilostazol added group) . Randomization will be done by the minimization method, controlling for the following factors: Country(Korea vs China) and max IMT (≥2.0mm vs.<2.0mm).

Group A : HMGCoA reductase inhibitor continued

Group B : HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID

Group C : HMGCoA reductase inhibitor continued + Probucol 250 mg PO, BID +Cilostazol 100 mg PO, BID

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1) Subjects who are at least 20 y of age at the time of informed consent (male or female)
  • 2) Subjects with coronary heart disease longer than 3 months.
  • 3) Subjects being treated with HMGCoA reductase inhibitors(Statins)
  • 4) Subjects with an max IMT equal to or greater than 1.2 mm
  • 5) Subjects with an LDL-Cholesterol less than 200mg/dl
  • 6) Subjects whose voluntary written informed consent is obtained for participation in this study

Exclusion Criteria:

  • 1) Subjects who took probucol within 6 months before participation of the study
  • 2) Subjects who took cilostazol within 3 months before participation of the study
  • 3) Subjects with a history of hypersensitivity to probucol or cilostazol
  • 4) Subjects with homozygous familial hyperlipidemia*
  • 5) Subjects with a triglyceride ( TG) level greater than 400mg/dL at screening
  • 6) Subjects with uncontrolled diabetes : HbA1c level greater than 9%
  • 7) Subjects with New York Heart Association (NYHA) classification: Class Ⅲ and Ⅳ
  • 8) Subjects with a QTc interval greater than 450msec(male) 470msec(female)
  • 9) Subjects with serious ventricular arrythmias (frequent episodes of multifocal ventricular extrasystole)
  • 10) Subjects with atrial fibrillation (including paroxysmal AF)
  • 11) Subjects with unstable angina
  • 12) Subjects with liver and kidney functions that satisfy the following criteria - AST or ALT >100 IU/L, serum creatinine >1.5 mg/dL
  • 13) Subjects who are participating in another clinical trial
  • 14) Subjects with pregnant or possibly pregnant without appropriate contraception control. Appropriate contraception control means that Oral contraception for greater than 4 weeks, surgical contraception including loop insertion, condom use etc. Women who has no possibility of pregnancy because of surgery or menopause should not be regarded the subject with possibly pregnant
  • 15) Subjects with clinically significant disorders of blood coagulation
  • 16) Subjects who are not considered by the physicians to be appropriate to participate in this trial for any other reason
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01291641

Contacts
Contact: Byung-Hee Oh, M.D +82-2-2072-3345 ohbhmed@snu.ac.kr
Contact: Hyun-Jae Kang, M.D. nowkang@snu.ac.kr

Locations
Korea, Republic of
Dong-A Medical Center Recruiting
Seogu, Busan, Korea, Republic of, 602-715
Contact: Moo-Hyun Kim, M.D.         
Principal Investigator: Moo-Hyun Kim, M.D.         
Samsung Medical Center Recruiting
Seoul, Gangnam-Gu, Korea, Republic of, 135-710
Contact: Jeong-Euy Park, M.D         
Principal Investigator: Jeong-Euy Park, M.D.         
Seoul National University Bundang Hospital Recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
Contact: Cheol Ho Kim, M.D.         
Contact: In-Ho Chae, M.D.         
Principal Investigator: Cheol-Ho Kim, M.D.         
Sub-Investigator: In-Ho Chae, M.D.         
Sub-Investigator: Gu-Yeong Jo, M.D.         
Boramae Medical Center Recruiting
Dongjak-Gu, Seoul, Korea, Republic of, 156-707
Contact: Sang-Hyun Kim, M.D.         
Contact: Jae-Bin Seo         
Principal Investigator: Sang-Hyun Kim, M.D         
Sub-Investigator: Jae-Bin Seo         
Seoul National University Hospital Recruiting
Jongno-gu, Seoul, Korea, Republic of, 110-744
Contact: Byung-Hee Oh, M.D.    +82-2-2072-3345    ohbhmed@snu.ac.kr   
Contact: Hyun-Jae Kang, M.D.       nowkang@snu.ac.kr   
Principal Investigator: Byung-Hee Oh, M.D.         
Sub-Investigator: Hyun-Jae Kang, M.D.         
Sub-Investigator: Hyung-Kwan Kim, M.D.         
Sponsors and Collaborators
Seoul National University Hospital
Korea Otsuka Pharmaceutical Co.,Ltd.
Investigators
Study Chair: Byung-Hee Oh, M.D. Seoul National University Hospital
Principal Investigator: Cheol Ho Kim, M.D. Seoul National University Bundang Hospital
Principal Investigator: Sang-Hyun Kim, M.D. SMG-SNU Boramae Medical Center
Principal Investigator: Moo-Hyun Kim, M.D. Dong-A medical center
  More Information

Publications:

Responsible Party: Byung Hee Oh/Professor, Department of Internal Medicine, Seoul National University Hospital, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01291641     History of Changes
Other Study ID Numbers: IMT-01
Study First Received: January 31, 2011
Last Updated: July 1, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:
Hyperlipidemias
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Probucol
Cilostazol

Additional relevant MeSH terms:
Hyperlipidemias
Coronary Artery Disease
Coronary Disease
Heart Diseases
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Cilostazol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Probucol
Anti-Asthmatic Agents
Anticholesteremic Agents
Antimetabolites
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Central Nervous System Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 21, 2014